Recently, natural or modified L-nucleoside are attracting attention as antiviral agents. Some L-nucleosides such as L-thymidine, L-2′-thiacytidine (3TC) and L-2′,3′-dideoxycytidine (L-ddC) are much less toxic and have better antiviral activity than their D-isomers. In addition, L-nucleosides have good effect in antisense oligonucleotide therapy.
For the above reasons, many attempts have been made to synthesize L-nucleosides effectively which cannot be obtained as natural products. The efforts has been being focused to economic and mass-produceable preparation method for the derivatives of L-sugar, particularly, 2-deoxy-D-ribose and L-ribose which can be used as key intermediates of L-nucleosides.
Some synthetic methods for 2-deoxy-L-ribose are known from D-ribose, L-arabinose or L-ascorbic acid. (WO 9839347, CS 274394B1, Nucleosides Nucleotidees 1999, 18 (11 & 12), 2357-2365, Tetrahedron: Asymmetry 2000, 11, 1869-176, Org. Lett 1999, 1 (10), 1517-1519).
In these methods, however, expensive or highly toxic reagents are used; difficult separation and purification is required; the overall yield is low; all which are obstacles to the application in the large-scale synthesis.